title: Identification of circulating microRNA signatures for breast cancer detection.
abstract: OBJECTIVE
  There is a quest for novel noninvasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA (miRNA) signatures using a cohort of Asian Chinese patients with breast cancer, and to compare miRNA profiles between tumor and serum samples.
  
  
  METHODS
  miRNA from paired breast cancer tumors, normal tissue, and serum samples derived from 32 patients were comprehensively profiled using microarrays or locked nucleic acid real-time PCR panels. Serum samples from healthy individuals (n = 22) were also used as normal controls. Significant serum miRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n = 132) and healthy controls (n = 101).
  
  
  RESULTS
  The 20 most significant miRNAs differentially expressed in breast cancer tumors included miRNA (miR)-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Only 7 miRNAs were overexpressed in both tumors and serum, suggesting that miRNAs may be released into the serum selectively. Interestingly, 16 of the 20 most significant miRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a, and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these miRNAs exhibited areas under the curves of 0.90 to 0.91.
  
  
  CONCLUSIONS
  The clinical use of miRNA signatures as a noninvasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers.
authors.affiliation: Division of Medical Sciences, National Cancer Centre, Singapore.
authors.forename: Maurice
authors.initials: M
authors.lastname: Chan
authors.forename: Chiew Suan
authors.initials: CS
authors.lastname: Liaw
authors.forename: Shen Mo
authors.initials: SM
authors.lastname: Ji
authors.forename: Hwee Huang
authors.initials: HH
authors.lastname: Tan
authors.forename: Chow Yin
authors.initials: CY
authors.lastname: Wong
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Gay Hui
authors.initials: GH
authors.lastname: Ho
authors.forename: Ann Siew-Gek
authors.initials: AS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen